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目的:探讨塞来昔布联合全反式维甲酸抑制结肠癌SW620细胞增殖和促进凋亡的作用及机制。方法:不同浓度塞来昔布和全反式维甲酸作用SW620细胞48或72 h后应用MTT法和流式细胞仪分别检测细胞的增殖抑制和凋亡率,Western Blot检测细胞AKT、p-AKT及survivin的表达。结果:与单药作用相比,塞来昔布和全反式维甲酸联合作用可明显增强对SW620的增殖抑制和促进凋亡作用(P均<0.01)。Western Blot提示全反式维甲酸和塞来昔布联合作用SW620细胞可抑制AKT活性,下调p-AKT和survivin蛋白表达。结论:塞来昔布在抑制结直肠癌细胞增殖和促进其凋亡中与全反式维甲酸起协同作用,抑制AKT磷酸化、阻断PI3K/Akt通路和下调survivin是其可能作用机制。此结果有望为临床提供可行的联合用药方案,推广维甲酸的诱导分化和凋亡治疗。
Objective: To investigate the effect of celecoxib combined with all-trans retinoic acid on the proliferation and apoptosis of human colon cancer cell line SW620. Methods: After treated with different concentrations of celecoxib and all-trans retinoic acid for 48 or 72 h, MTT assay and flow cytometry were used to detect the proliferation and apoptosis of SW620 cells respectively. Western Blot was used to detect the expression of AKT and p-AKT And survivin expression. RESULTS: Compared with monotherapy, the combination of celecoxib and all-trans retinoic acid significantly enhanced the proliferation and apoptosis of SW620 cells (all P <0.01). Western Blot suggested that all-trans retinoic acid and celecoxib combined SW620 cells can inhibit AKT activity, down-regulation of p-AKT and survivin protein expression. CONCLUSION: Celecoxib synergizes with all-trans retinoic acid in inhibiting the proliferation and promoting apoptosis of colorectal cancer cells, inhibiting its phosphorylation, blocking PI3K / Akt pathway and down-regulating survivin. This result is expected to provide a viable combination regimen for clinical practice to promote the induction of differentiation and apoptosis of retinoic acid.